The single feature most characteristic of rheumatoid arthritis is tumorlike proliferation of the synovium. During the past year, we have obtained additional evidence that platelet-derived growth factor, particularly a PDGF-B-like polypeptide, and heparin binding fibroblast growth factors play a role in regulating the growth and function of the connective tissue cells in diseased synovium. We have also begun to study the role of neuropeptides in rheumatoid synovitis. Evidence has been obtained that locally produced corticotropin releasing hormone plays an important proinflammatory role in the disease process. These data provide additional evidence for interactions of the immune and central nervous systems in regulating inflammatory disease. In addition, upregulated expression of other important inflammatory regulators such as cyclooxygenase and uteroglobin has been demonstrated. All of these factors are expressed at low levels in synovium from osteoarthritic patients.